An adoptive immunotherapy using T cells (CAR-T), which express a chimeric antigen receptor (CAR) targeting a tumor-associated antigen, has been reported to exert a powerful antitumor effect, and rapidly developed in recent years. In particular, development of a CAR targeting CD19 has been advanced. The CAR exerts remarkable effects in clinical trials and highly attracts attention. In general, the CAR is a protein having a single-stranded polypeptide derived from an antibody and retaining the binding ability to an antigen, a single-chain antibody (scFv), as a target binding domain and having an intracellular signaling domain linked thereto. Typically, an antibody polypeptide, in which Fv regions of an immunoglobulin heavy-chain (H chain) and light-chain (L chain) fragments are linked, is used as a target binding domain (Non Patent Literature 1).
The CAR-T therapy is highly effective; however, side effects are frequently produced, as is found in clinical trials. Particularly, since a mouse-derived single-chain antibody (scFv) is used as an antigen-binding domain, in most cases, an undesirable immune response occurs, leading to a risk of inducing serious anaphylactic shock. Accordingly, it is required to provide a CAR having an excellent effect and safety. In view of this, use of a ligand-type CAR has been proposed as an alternative to conventional antibody-type CARs (Non Patent Literature 2).